This module shows: 1) how a target synthesis may be designed using retrosynthetic analysis; and 2) how modern reactions can be applied to the synthesis of target organic molecules.

• understand the use of transition metal catalysts in organic synthesis with emphasis on stereoselective transformations;
• perform a retrosynthetic analysis and propose a forward synthesis for any given target molecule;
• design synthetic routes for target molecules based on an understanding of chemical reactivity and knowledge of organic reactions as taught in modules CH4103 and CH4203;
• design syntheses of target organic molecules, including the use of protective groups as required for compatibility of reactivity.

22 x 1 h Lectures, 3 x 1 h Workshops, 2 x 1 h Tutorials

Advanced organic synthesis methods: The student will practice retrosynthetic analyses in a complex setting.

Development of the skill to include advances oxidation strategies (Epoxidations, dihydroxylations) in total syntheses and retrosyntheses.

Development of stereochemical thinking by practicing asymmetric oxidations.

The module is summatively assessed via in course assessments.

There is no examination for this module.

Retrosynthetic analysis

Introduction to disconnections and the logic of synthesis

C-X disconnections – halides, ethers, sulphides and amines and 1,2- & 1,3-difunctionalised compounds

C-C disconnections and synthesis using carbonyl group, including alkene synthesis, enolate alkylation selectivity

Synthesis of 1,3-, 1,4- and 1,5-dicarbonyl compounds

Use of protecting groups when chemoselectivity issues arise

Manipulation of double bonds, ring opening, ring expansion and ring formation techniques

Pericyclic reactions

Electrocyclic reactions, Cycloadditions, Sigmatropic rearrangements (Diels-Alder reaction, 1,3-dipolar cycloaddition, Claisen rearrangement etc.)

Palladium-catalysed coupling methods

Disconnection for the synthesis of polyunsaturated systems

Definitions of Heck, Suzuki-Miyaura, Kumada, Negishi and Sonogashira methods

Catalytic cycle summary and key differences within these

Perspective on utility, practicalities etc.

Selected applications in synthesis, with emphasis on the retrosynthetic features and stereoselective synthesis

Precursor synthesis where appropriate

Metathesis

Definition and emphasis on catalyst types for both ring closure (ene-ene, ene-yne and yne-yne) and cross metathesis; experimental methods; brief mention of utility in polymer synthesis and total synthesis

Modern oxidative transformations

Epoxidations (Sharpless Asymmetric Epoxidation, Jacobsen Epoxidation)

Dihydroxylation; AD-mix; related osmylation methods; synthetic utility (examples).